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. 2008 Feb 6;3(2):e1555. doi: 10.1371/journal.pone.0001555

Table 3. In-silico mutation experiments for validation.

No. Species Organisms Exp. Experimental effects Effects in our models
1. Mad2 H. s. D -Impaired MSAC [32] - MSAC fails to arrest
Mad2 M. D -Unable to arrest [72] & no Cdc20 sequestering.
Mad2 H. s. & M. D -Defective MSAC [73] - [APC:Cdc20] very high.
Mad2 H. s. D -Unable to bind Cdc20 or Mad1 [74]. More refs.: [31], [40], [108] [1], [34], [109]-[111].
2. Mad2 H.s. O -Activates the MSAC [25] -Activates the MSAC
Mad2 S.p. O -Blocks mitosis [90] & full Cdc20 sequestering. -[APC:Cdc20] very low.
3. Mad1 H.s. D - MSAC inactivation & aneuploidy [75]. - MSAC fails to arrest & no Cdc20 sequestering.
Mad1 S.p. D - cell death [76]. More refs.: [77]-[79]. -[APC:Cdc20] very high.
4. BubR1 H.s. D -Reduced MSAC function, Reduced MSAC binding to Cdc20:C-Mad2 [47]. -MSAC fails to arrest.
-[APC:Cdc20] very high.
BubR1 M. D -Increased polyploidy [82]. More refs.: [83], [84].
5. Bub3 M. D -Fails to arrest [80], [81]. -MSAC fails to arrest.
-[APC:Cdc20] very high.
6. Cdc20 S.c. O -Allows cells with a depolymerized spindle or damaged DNA to leave mitosis [91]. -MSAC fails to arrest.
-[APC:Cdc20] very high.
-Impairment MSAC and aneuploidization in oral cancer [112].
7. Cdc20 H.s. D -Reduced binding to Mad2, selective disruption from Mad2 [85]. - blocks mitosis.
-[APC:Cdc20] very low.
Cdc20 S.p. D -Arrest in metaphase [113].
8. Bub1 Drosophila Inh. -Chromosome missegregation [86]. -MSAC fails to arrest.
-[APC:Cdc20] very high.
Bub1 H.s. Inh. -Disruption of Bub3 localization, disruption of Bub3 binding to BubR1 [81].
9. Aurora B Xenopus Inh. -Overriding the MSAC function, perturbs MTs dynamics [87]. -MSAC fails to arrest.
-[APC:Cdc20] very high.
Aurora B S.c. Inh. -Unregulated MTs,
- MSAC fails to arrest [88], [89]
10. APC (units) Cdc26, apc9 Cdc6,doc1 S.p. D -Disruption of complex association [92], [93], More refs.: [114]. -Activates the MSAC.
-[APC:Cdc20] very low.

Abbreviations: D for deletion or knockdown experiments, O for over-expression experiments, and Inh. for inhibition; S.c., Saccharomyces cerevisiae; S.p., Schizosaccharomyces pombe; H. s., Homo sapiens(Human); and M., Murine.